Using 7‑Tesla fMRI and a placebo paradigm, University of Sydney researchers mapped how the human brainstem modulates pain by body region. The study, published in Science on August 28, 2025, outlines a somatotopic system centered on the periaqueductal gray and rostral ventromedial medulla and suggests avenues for localized, non‑opioid treatments.
Researchers at the University of Sydney report that the human brainstem contains a spatially organized system for controlling pain that varies by the body region affected, potentially enabling more precise therapies. The findings were published in Science on August 28, 2025.
In experiments with 93 healthy adults, the team used ultrahigh‑field 7‑Tesla functional MRI alongside a placebo‑analgesia conditioning design: a cream was applied to specific skin sites while the heat stimulus was surreptitiously lowered to create an expectation of relief, then restored to the original temperature. When full heat was reapplied, about 61% of participants continued to report less pain at the conditioned sites, demonstrating localized placebo analgesia, according to the University of Sydney’s summary of the work.
The imaging results showed somatotopic organization in two key brainstem structures. Upper portions of the periaqueductal gray (PAG) and the rostral ventromedial medulla (RVM) were preferentially engaged during facial pain relief, whereas lower sections were recruited during arm and leg pain relief, the authors report. The Science paper identifies the lateral PAG and its descending projections to the RVM as central to this spatially specific control.
“This is the first time we’ve seen such a precise and detailed pain map in the human brainstem, showing us that it tailors pain relief to the specific part of the body that’s experiencing it,” said lead author Dr. Lewis Crawford of the School of Medical Sciences and the Brain and Mind Centre. Senior author Professor Luke Henderson added, “We now have a blueprint for how the brain controls pain in a spatially organized way. This could help us design more effective and personalized treatments, especially for people with chronic pain in a specific area of their body.”
The work may help steer development of non‑opioid therapies. While opioid analgesia can produce widespread effects, the researchers highlight evidence that a lateral PAG circuit may support more localized control and could be linked to cannabinoid mechanisms, according to the University of Sydney release.
Methodological details reported by the university indicate that heat stimuli were calibrated individually to evoke moderate pain (participants rated intensity on a 0–100 scale), typically corresponding to temperatures between roughly 40°C and 50°C. According to the same account, two 7‑Tesla scanners are available in Australia; the ultrahigh‑field system enabled the group to resolve activity across subregions of the PAG and RVM.
The study builds on decades of brainstem pain‑modulation research led by co‑author Professor Kevin Keay, the university noted. The authors and external commentators in Science emphasize that translating these mechanistic insights to clinical practice will require further work, but the map provides a targetable framework for assessing whether prospective drugs or non‑invasive interventions act in the intended brainstem loci.
